PROJECT SUMMARY/ABSTRACT New technologies that modulate brain function have tremendous potential for alleviating the persistent burden of depression and other neuropsychiatric disorders, but also raise challenging ethical and societal questions regarding self-ownership and control over our thoughts, emotions and actions. For these reasons, the President?s Bioethics Commission and other experts have called for the integration of ethics and neuroscience from the earliest stages of research. Such integration requires collaboration across humanistic and scientific disciplines; and for this work to effectively shape the future ethical development of the field, it must also actively engage patients and researchers at the forefront of novel neurotechnologies. The need for ethical integration in neuroscience will be addressed by a cohesive interdisciplinary team with expertise in neuroscience, clinical care, law, philosophy and social science. This work will be embedded in one of the two teams funded by DARPA as part of the BRAIN Initiative to develop implantable ?closed-loop? devices that will both monitor and adaptively modify brain systems involved in mood and behavior regulation. Such embedding will facilitate the overall goal of enabling the successful development and adoption of needed new treatments for neuropsychiatric illness by recognizing, communicating, and incorporating the ethical concerns of patients and other stakeholders into the design of neurotechnological therapies. Innovative comparative ethnographic techniques will be applied in populations at the clinical frontier of human neurotechnology, in pursuit of three specific aims: 1) Elicit ethical concerns in existing clinical applications of closed-loop neuromodulation; 2) Elicit ethical concerns in investigational research on closed-loop neuromodulation of mood; and 3) Assess the influence of disciplinary backgrounds on investigators? evaluation of ethical concerns. Aim 1 will focus on clinic patients with drug-resistant epilepsy undergoing NeuroPace stimulation, the only form of closed-loop brain modulation currently approved for clinical use. Aim 2 will focus on research patients with Parkinson?s disease and comorbid depression in a DARPA-sponsored research project to measure and modify neural correlates of mood using a novel implanted deep brain stimulator. Aim 3 addresses how these patient experiences and concerns can be incorporated in clinicians? and researchers? views about the ethical development of neurotechnology. The approach is innovative, as embedding an interdisciplinary team with expertise in advanced qualitative methods directly in a DARPA-funded neurotechnology program will facilitate the incorporation of ethical concerns in the earliest stages of technology development. The proposed research is significant, because it addresses core ethical and societal concerns that will affect the acceptability of closed-loop neuromodulation of mood, a core element of the BRAIN Initiative, and that will likely continue to grow along with our advancing ability to manipulate the human brain.